A magnetically separable heterogeneous deallylation catalyst: [CpRu(n 3-C3H5)(2-pyridinecarboxylato)]PF6 complex supported on a ferromagnetic microsize particle Fe3O 4@SiO2

Article abstract of DOI:10.1002/ejoc.200801166

The highly reactive and chemoselective homogeneous deallylation catalyst CpRu(η³-C₃H₅)(4-substituted-2- pyridinecarboxylato) was immobilized on microsize spherical Fe₃O ₄@SiO₂ particles. The resultant heterogeneous catalyst displays high saturation magnetization, weak coercive forces and high levels of dispersibility. The catalyst has increased the utility of deallylation by allowing the reaction to be conducted without extra additives. The only co-product of the reaction is a volatile allyl ether compound. Here, we demonstrate the efficient deallylation and separation of highly polar multifunctional compounds as well as multiple rounds of catalyst recycling without significant loss of reactivity. The usefulness of this catalyst has been confirmed by the synthesis of a triribonucleotide 3-5 U.

Full text of DOI:10.1002/ejoc.200801166

SHORT COMMUNICATION
DOI: 10.1002/ejoc.200801166
A Magnetically Separable Heterogeneous Deallylation Catalyst:
[CpRu(η3-C3H5)(2-pyridinecarboxylato)]PF6 Complex Supported on a
Ferromagnetic Microsize Particle Fe3O4@SiO2
Takuya Hirakawa,[a] Shinji Tanaka,[a] Naoki Usuki,[b] Hisao Kanzaki,[b] Mikio Kishimoto,[b]
and Masato Kitamura*[a]
Keywords: Sustainable chemistry / Supported catalysts / Ruthenium / Protecting groups / Magnetic particles / π-Allyl
complexes
The highly reactive and chemoselective homogeneous
deallylation catalyst
CpRu(η3-C3H5)(4-substituted-2-
reaction is a volatile allyl ether compound. Here, we demon-
strate the efficient deallylation and separation of highly polar
multifunctional compounds as well as multiple rounds of cat-
alyst recycling without significant loss of reactivity. The use-
fulness of this catalyst has been confirmed by the synthesis
of a triribonucleotide 3–5 U.
pyridinecarboxylato) was immobilized on microsize spherical
Fe3O4@SiO2 particles. The resultant heterogeneous catalyst
displays high saturation magnetization, weak coercive forces
and high levels of dispersibility. The catalyst has increased
the utility of deallylation by allowing the reaction to be con-
ducted without extra additives. The only co-product of the
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2009)
of the catalyst is highly desirable. One apparent solution to
this problem is the immobilization of a homogeneous cata-
lyst to an insoluble material. Indeed, a variety of suitable
Introduction
Over the past two decades there has been significant pro-
gress in the field of homogeneous catalysis.[1] As a result,
many organic transformations are now achieved under cata-
lytic conditions, realizing high efficiency in terms of atom
economy, E factor, safety and operational simplicity.[2,3]
Our deallylation and allylation catalyst, [CpRu(η3-C3H5)(2-
quinolinecarboxylato)]PF6 (1), has also increased the utility
of the allyl moiety as a suitable protecting group.[4] Removal
of the allyl group from 2 proceeds in alcoholic solvents,
typically in methanol, without the need of any extra nucleo-
philes such as amines, metal hydrides and enolates that are
required for conventional Pd-based methods.[5] The only co-
product in the reaction is the volatile allyl ether, which can
be easily removed by evaporation to afford the final product
3. However, separation of the catalyst from the product is
still a major issue. Contamination of the product after the
catalytic process reduces the efficiency of product isolation.
Indeed, this problem is particularly serious for the synthesis
of highly polar bio-related polymers such as peptides and
oligonucleotides.[6] From an economic perspective, recycling
[a] Research Center for Materials Science and Department of
Chemistry, Nagoya University,
Chikusa, Nagoya 464-8602, Japan
Fax: +81-52-789-2958
E-mail: kitamura@os.rcms.nagoya-u.ac.jp
[b] R&D Division, Hitachi Maxell, Ltd.,
1 Koizumi Ohyamazaki-cho, Otokuni-gun, Kyoto 618-8525,
Japan
Supporting information for this article is available on the
WWW under http://www.eurjoc.org or from the author.
Scheme 1.
Eur. J. Org. Chem. 2009, 789–792
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789

M. Kitamura et al.
SHORT COMMUNICATION
organic and inorganic supports have already been re-
Table 1 lists the representative results of deprotection of
ported.[7] This paper describes a new type of heterogeneous alcohol 3 catalyzed by 4. AOC-protected 2-phenylethan-1-
deallylation catalyst, [Fe3O4@SiO2–L–CpRu(η3-C3H5)] (4), ol (2a) was converted to 2-phenylethan-1-ol (3a) in
which consists of ferromagnetic particles and a cationic Ͼ99%[16] within 1 h {Entry 1; [2a] = 100 m, substrate/cat-
CpRu(η3-C3H5) complex immobilized through the 4-[5- alyst ratio (S/C) = 100, CH3OH, shaken at 30 °C}. Under
(C2H5O)3Si(CH2)5NHCO]-2-pyridinecarboxylate
monoanionic ligand 5 (Scheme 1).
these conditions the catalyst particles are well dispersed.
Nevertheless, the catalyst can be quickly collected by appli-
cation of a magnetic field. There was only a slight decrease
in reactivity after 10 rounds of catalyst recycling (En-
try 4).[14] During each cycle Ru leaching was below 0.2%.
The reaction proceeds even with an S/C ratio of 10000 (En-
try 6). Ethanol and 2-propanol were the solvents of choice
(Entries 7, 8), but the reactivity was significantly reduced in
tert-butyl alcohol (Entry 9). Water, DMF, THF, dichloro-
methane, and acetonitrile are usable as a co-solvent of
methanol (Entries 10–14). Phenol as well as primary, sec-
ondary, and tertiary alcohols are efficiently deprotected
from the AOC-protected forms 2a–d (Entries 1 and 15–17).
Bn, Bz, MOM, and TBDPS groups in compounds 2e–h re-
main intact under all heterogeneous reaction conditions
(Entries 18–21). Allyl carboxylate 2i as well as the less reac-
tive allyl ether 2j are also suitable substrates (Entries 22,
23).
Results and Discussion
The Fe3O4@SiO2–L–CpRu(η3-C3H5) catalyst 4 has a
microsize spherical shape and possesses characteristic ferro-
magnetic properties.[8] Each particle contains a few tens of
Fe3O4 beads (diameter of ca. 200 nm) with a catalyst sup-
ported on the silicate surface by covalent Si–O bonds, which
significantly reduces leaching of the ligand moiety.[9] The
Ͼ100 nm size of the Fe3O4 particles increases the saturation
magnetization. Furthermore, the spherical shape of the par-
ticles in the absence of magnetic anisotoropy weakens the
coercive forces. Together, these factors avoid self-aggrega-
tion,[10] which is a serious problem associated with magnetic
nanoparticles. The microsize of the particles maintains the
appropriate dispersibility, although catalyst separation can
be easily achieved by application of an external magnetic
field. The particles are readily redispersed due to the rela-
tively weak van der Waals force. This is also advantageous
in comparison to nanoparticles, which are attracting con-
siderable attention at the moment.[8,11] The Fe3O4@SiO2
particles were prepared according to the Hitachi method.[12]
The ligand moiety 5 was synthesized in 71% yield by dehy-
drative condensation of 2-allyl hydrogen pyridine-2,4-di-
carboxylate[13,14] with 5-(triethoxysilyl)pentan-1-amine.[15]
Table 1. Catalytic cleavage of allyl esters and ethers by using Fe3O4-
@SiO2–L–CpRu(η3-C3H5) catalyst 4.[a]
Entry Substrate
Solvent
Conversion (%)[b]
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2a
2b
2c
2d
2e
2f
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
C2H5OH
Ͼ99
Ͼ99[c]
Ͼ99[d]
Ͼ99[e]
Ͼ99[f]
Ͼ99[g]
Ͼ99[h]
Ͼ99[i]
Ͼ99[j]
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Compound
5 was then immobilized on 50 mg of
i-C3H7OH
t-C4H9OH
CH3OH/H2O (1:1)
CH3OH/DMF (1:1)
CH3OH/THF (1:1)
CH3OH/CH2Cl2 (1:1)
CH3OH/CH3CN (1:1)
CH3OH
Fe3O4@SiO2 ([5] = 50 m, toluene, reflux, 32 h), giving
Fe3O4@SiO2–L–CH2CH=CH2. Complexation of the pyr-
idine region on Fe3O4@SiO2–L–CH2CH=CH2 with
[CpRu(CH3CN)3]PF6 (ca. 2.5 mol-equiv. for the pyridine
moiety, 30 °C, 2 h) followed by magnetic separation af-
forded Fe3O4@SiO2–L–CpRu(η3-C3H5) (4). ICP-OES
analysis of the solution phase before and after immobiliza-
tion shows a diminution of Ru that corresponds to the
amount of complex loaded onto the solid support (78–
84 µmol/g).[14] An SEM image of uniform particles (dia-
meter of ca. 5 µm) is given in Figure 1.
99
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
Ͼ99[k]
Ͼ99
Ͼ99
Ͼ99
Ͼ99
Ͼ99
2g
2h
2i
Ͼ99
2j
98[l]
[a] All reactions were carried out under the following conditions,
unless otherwise specified: [2] = 100 m; 50–90 µmol scale; 10 mg
of 4 (0.52–0.85 µmol depending on the catalyst loading on Fe3O4-
1
@SiO2); S/C = 100; 30 °C; 1 h. [b] Determined by H NMR spec-
troscopy.[14,16] [c] Isolated yield in a reaction of 177 mg of 2a.[14] [d]
Use of 4 after 4 recycles. [e] Use of 4 after 9 recycles. Reaction
time: 2 h. [f] [2a] = 500 m; S/C = 1000; 11 h. [g] [2a] = 500 m;
S/C = 10000; 50 °C; 15 d. [h] 2 h. [i] 6 h. [j] 3 d. [k] 2 h. [l] 8 h.
A dipeptide Fmoc-Phe-Asp(allyl)-OtBu (6) was quantita-
tively converted into the corresponding Fmoc-Phe-Asp-
OtBu (7) without affecting the tBu ester and Fmoc groups
Figure 1. SEM image of Fe3O4@SiO2–L–CpRu(η3-C3H5) catalyst 4. under standard reaction conditions. The existence of a po-
790
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Eur. J. Org. Chem. 2009, 789–792

Magnetically Separable Heterogeneous Deallylation Catalyst
geneous state. However, isolation yield of the final product
as the ammonium salt is generally less than 95%. Use of
Fe3O4@SiO2–L–CpRu(η3-C3H5) complex 4 solved this
problem because of the easy separation of the product from
the catalyst and an excess amount of diethylamine by sim-
1
ply applying an external magnetic field. H NMR spectra
of 9 obtained by homogeneous and heterogeneous catalysis
and of the final ammonium salt 10 are shown in Figure 2.
Conclusions
We have developed a heterogeneous deallylation catalyst
by immobilization on microsized spherical SiO2 particles
containing Fe3O4. The resultant catalyst displays high satu-
ration magnetization, weak coercive forces and high disper-
sibility. The catalyst can be removed from the reaction mix-
ture by simple magnetic separation and is recyclable.
Furthermore, the catalyst can operate in alcoholic solvents
in the absence of any extra additives. The heterogeneous
version of the catalyst should further enhance the utility of
the CpRu-catalyzed deallylation in protecting group chem-
istry and in organic synthesis.
lar peptide linkage exerts little influence on the reactivity.
A triuridine 3–5 U derivative 8, which is fully protected by
allyl groups at C(2Ј) and phosphoric acid, was successfully
deprotected and isolated as the diethylammonium salt 10.
The acid form of 3–5 U (9) is unstable. Therefore, deprotec-
tion at 30 °C for Ͻ1 h followed by diethylamine treatment
is required. High loading of catalyst (8 mol-% per allyl
group) can realize quantitative deprotection by using
[CpRu(η3-C3H5)(2-quinolinecarboxylato)]PF6 in a homo-
Experimental Section
General Procedure for the Catalytic Removal of the Allyl Group in 2
by Using 4: Fe3O4@SiO2–L–CpRu(η3-C3H5) particles (4; 10.6 mg,
78.5 µmol/g, 0.832 µmol) were placed in a dry and argon-filled 5-
mL tube equipped with a Young’s tap. Into this vessel a 100 m
solution of allyl 2-phenylethyl carbonate (2a) in methanol
(0.832 mL, 0.0832 mmol), degassed three times by freeze-thaw cy-
cles, was added through an inlet capped by a septum rubber under
an argon stream. After the rubber was replaced with a Young’s
tap, the suspension was shaken at 30 °C for 1 h. The particles were
magnetically separated, and the liquid phase was concentrated un-
der reduced pressure (100 Torr) to give a crude product. The con-
version and purity were determined to be Ͼ99% by 1H NMR
analysis.[14,16]
Supporting Information (see footnote on the first page of this arti-
cle): The details of catalyst preparation and general procedures for
the deallylation.
Acknowledgments
This work was supported by the Ministry of Education, Culture,
Sports, Science and Technology, Japan through a Grant-in-Aid for
Scientific Research on Priority Areas (No. 19028024, “Chemistry
of Concerto Catalysis”).
1
Figure 2. H and 31P NMR spectra of 3–5 U (9) and the diethyl-
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Eur. J. Org. Chem. 2009, 789–792
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the conversion corresponds approximately to the yield.
Received: November 25, 2008
Published Online: January 12, 2009
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